2nd Generation Adenovirus
2nd generation adenovirus [E1-, E3-, pol-] infects cochlear
hair cells without effecting transduction.
We have determined which viral vector could infect hair cells, and which promoters could drive expression of transgenes in the infected hair cells. We found that adeno-associated virus (AAV) was able to deliver mRNAs to blood vessels and certain nerve fibers of the cochlea, but was not able to infect cochlear hair cells using a variety of promoter constructs.
We found that first-generation adenovirus [E1-, E3-] could infect cochlear hair cells, yet was ototoxic, similar to the toxicity observed in cultured hair cells. However, we determined that a modified adenovirus [E1-,E3-, E2b-] could infect cochlear hair cells both in culture and in vivo with no loss of either transduction currents or cochlear function. 2nd generation adenovirus is able to transfect cochlear and vestibular cultures with no loss of stereocilia bundle integrity nor loss of transduction channel efficacy when tested as long as 2 weeks post viral transfection.
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